Industries · Biological medicinal products

Biological medicinal products step by step.

Products made by or from living organisms. Below: the path of one batch as the rules describe it, what MALUTI records at each step, and every record type these documents ask for — built or not yet.

The path of a batch

Biological medicinal products · EU GMP Annex 2 · 21 steps

Your certificate, line by line →

Grown from a bank

Vaccines, recombinant proteins, monoclonals: everything that comes out of a culture. The annex answers the drift that repeated subculture brings with a system of two generations — a master bank and a working one — and then asks how many passages stand between that bank and the vial. A bank is held here as master or working, with the regime it answers to declared once; it is characterised and released, a container taken out of it does not go back, and a batch carries the passages back to its bank. The bank’s cold is not held yet.

Taken from a donor

From a person or an animal. The line has to run forward to the point of use and backward to the last healthy donation, and be kept for thirty years after expiry — the longest retention in the whole of volume 4. A donation is held here by two codes and no name. From it the line runs forward to every batch, consignment and receipt at the point of use, and from a batch back to its donations, with the thirty years counted from the products. Not held yet: the substances that touched the cells on the way, and the animal that several donations came from.

Before the first batch

Training is specific to what is grown here
Built in MALUTI

Everyone working where biological substances are made and tested — cleaning, maintenance and quality control included — trained and periodically retrained for these products in particular, including the measures that protect them and the environment.

Annex 2 §1
A change in someone’s health keeps them out, and it is recorded
Built in MALUTI

Health status taken into account for product safety, vaccination and regular checks where needed; a change in health that could affect the product precludes work in the production area, and the record of that is kept.

Annex 2 §2, §3
People do not walk from the live organisms to the rest
Not built yet

Movement of all personnel — quality control, maintenance and cleaning included — restricted on risk grounds, so that nobody passes from areas with live organisms, genetically modified organisms, toxins or animals to areas holding other products.

Not built: access is granted per room and every entry carries its time, so where a person went is known. The order they went in is not: nothing here refuses a second room because of the first one.

Annex 2 §4

The bank

Everything grown comes from a master and a working generation
Built in MALUTI

A system of master and working seed lots or cell banks, with the number of generations between the bank, the active substance and the finished product kept within what the authorisation allows.

Annex 2 §39, §40
A new bank is quarantined, characterised and released
Built in MALUTI

Quarantine and release procedures after a bank is established, with characterisation and testing for contaminants, evidence of stability and recovery documented, and records kept so that a trend can be read across the batches grown from it.

Annex 2 §42
The bank has an inventory, and its cold is recorded continuously
1 of 2 built

Sealed and clearly labelled containers at an appropriate temperature; a stock inventory kept; the storage temperature recorded continuously and the liquid nitrogen level monitored; every deviation from the set limits recorded with the action taken.

Annex 2 §45
What leaves the bank does not come back
Built in MALUTI

Stocks stored and handled under the same procedures and parameters, and containers once removed from the bank management system never returned to stock.

Annex 2 §47

The donor

The line runs from the donor to the point of use, and back
1 of 2 built

Full traceability from starting and raw materials — everything that touches the cells or tissues included — through to confirmation of receipt at the point of use, with the privacy of the person kept, and the records held for thirty years after the expiry date.

Annex 2 §28, §36
What the donor’s doctor learns later still reaches the product
Built in MALUTI

An arrangement with the supplier of tissues and cells for passing on health information that appears after the material was supplied, and that information taken into account in the recall procedure when it affects quality.

Annex 2 §36, §65
Source animals are under a health programme, and it is recorded
Not built yet

Adventitious agents monitored by an ongoing health programme and recorded; ill health investigated and the decisions documented; key criteria per species — age, weight, health status — defined, monitored and recorded; the withdrawal period of any treatment documented.

Annex 2 §20, §21, §24
A sick animal sends us back through everything it touched
1 of 2 built

A look-back procedure that decides whether the substance or product made from that animal’s material is still suitable, including retesting retained samples from earlier collections to find the last negative donation.

Annex 2 §20

Making it

A biological material carries its origin, not just its name
3 of 4 built

The source, origin and suitability of biological starting and raw materials clearly defined, with additional documentation on the distribution chain, the method of manufacture and the controls applied.

Annex 2 §26, §31
What counts as a batch is declared, not assumed
Built in MALUTI

Some product types need the batch defined specifically — for autologous and donor-matched material, the product made for the one person is the batch.

Annex 2 §27
Critical parameters are identified, validated and held
Built in MALUTI

Critical operational parameters and other inputs that affect quality identified, validated, documented and shown to stay within their requirements.

Annex 2 §49
Continuous monitoring belongs to the batch record
Built in MALUTI

Continuous monitoring of production processes such as fermentation where necessary, with that data forming part of the batch record.

Annex 2 §53
Treated product never meets untreated product
Built in MALUTI

Where a virus is inactivated or removed during manufacture, measures against recontamination of treated product by untreated; where inactivation is by a reagent, complete inactivation assured, including the surfaces that met the live culture.

Annex 2 §57, §58
A product made for one person says whose it is
2 of 3 built

Care in the preparation, printing, storage and application of labels; for autologous products the unique patient identifier and the words «for autologous use only» on the outer packaging, or on the immediate packaging where there is no outer one.

Annex 2 §63

Testing and release

In-process control carries more weight here than at the end
Built in MALUTI

In-process control testing performed at the stages that matter, because with biological products it does more for consistency than testing the finished product.

Annex 2 §66
An intermediate that waited is followed into the stability programme
Built in MALUTI

Where intermediates can be stored for days or weeks, finished batches made from material held for its maximum in-process period included in the on-going stability programme.

Annex 2 §67
Fourteen days or less: certified in two stages
Built in MALUTI

For a shelf life of fourteen days or less, a described release procedure naming who assesses what: a designated person reviews the batch records, the environmental data and the available results for the initial certification, and the authorised person certifies finally once the rest arrive; out-of-specification results afterwards are investigated and the actions documented.

Annex 2 §70
Variability and change are reviewed on a period, not on a whim
Built in MALUTI

Steps that reduce process variability reassessed during the product quality review, and change management periodically taking into account the cumulative effect of changes on quality, safety and efficacy.

Annex 2 §29, §48

What the rules ask, and what is built.

EU GMP Part I · EU GMP Annex 2, and the path of a batch above. 58 of 79 record types kept in MALUTI · 19 not built yet · 2 outside the software.

A record type in our catalogue is one thing a clause asks a site to record. Each is counted once, even when two documents or a step of the path ask for it. “Kept in MALUTI” covers what MALUTI does itself and the record it keeps of work your site does. The count shows what we have mapped, not a share of the regulation.

Not read into our catalogue yet, and not counted: Annex 14 (products derived from human blood or plasma). The operations they govern are counted here by Part I and Annex 2 alone.

Not built yet (19)

Keep a visitor policy with classes of person EU GMP ch. 2 §2.13
Use only starting materials that Quality Control has released EU GMP ch. 5 §5.34
Clear the work area and equipment before a processing operation starts EU GMP ch. 5 §5.40
Record who took material out of store for a run EU GMP ch. 5 §5.37
Derive the exposure limits behind a shared line EU GMP ch. 5 §5.20
Hold the periodic management review of the quality system EU GMP ch. 1 §1.6
Record the air pressure differences between rooms, and record what was decided when the warning fired EU GMP Annex 2 §12
Hold where a biological material came from — its source, its route through the supply chain, and the TSE assessment EU GMP Annex 2 §26, §31, §32
Start work on a material whose test has not come back, and hold the product's release until it does EU GMP Annex 2 §31, §36
Test container closure integrity — every fused container, a justified sample of the others EU GMP Annex 2 §61
Test critical gas and vent filters after use, record the others at intervals, and hold their maximum duration of use EU GMP Annex 2 §16
Keep the bank inventory, and record its temperature continuously EU GMP Annex 2 §45
Trace from the donor to the batch and from the batch to the point of use, and keep it for thirty years EU GMP Annex 2 §28, §36
Run the health programme for source animals, and record what it finds EU GMP Annex 2 §20, §21, §24
Look back from a sick source animal to everything made from its material EU GMP Annex 2 §20
Print the patient identifier and «for autologous use only» EU GMP Annex 2 §63
Deal with a spill of live organisms by its qualified method, and record the event EU GMP Annex 2 §55, §56
Hold each chromatography column as an item with a life span, a regeneration record and a sanitisation method EU GMP Annex 2 §59
Write down the reduced testing and retention strategy where there is not enough material for the normal one EU GMP Annex 2 §68

And one step of the path with nothing yet to record it — not counted above, because there is no record type for it in the catalogue yet:

People do not walk from the live organisms to the rest Annex 2 §4

Built in MALUTI (54)ShowHide

Record what a person is qualified by EU GMP ch. 2 §2.1
Keep the record of a consultant: name, address and service EU GMP ch. 2 §2.23
File fitness for work EU GMP ch. 2 §2.16
Record training and its expiry EU GMP Annex 2 §1
Assess periodically whether training actually worked EU GMP ch. 2 §2.11
Keep training programmes approved by the head of Production or of Quality Control EU GMP ch. 2 §2.11
Grant access to rooms EU GMP ch. 3 §3.5
Keep an organisation chart showing who answers to whom EU GMP ch. 2 §2.2
Write down the duties and the authority of a responsible position EU GMP ch. 2 §2.3
Declare what each room must hold, and watch it EU GMP ch. 3 §3.19
Register equipment and its qualification EU GMP ch. 3 §3.34, §3.41
Keep the use and cleaning log of each machine EU GMP ch. 4 §4.31
Examine each container: labels, damage, broken seals EU GMP ch. 5 §5.30
Run an identity test on every batch received EU GMP ch. 5 §5.35
Hold incoming material in quarantine until released EU GMP Annex 2 §42
Hold the approved manufacturing formula, with its versions and its effective date EU GMP ch. 4 §4.17, §4.3
Define a process as data, with its limits EU GMP Annex 2 §49
Start and run a process EU GMP Annex 2 §66
Investigate a significant deviation from expected yield EU GMP ch. 5 §5.44
Run an on-going stability programme EU GMP ch. 6 §6.27–6.31
Trend results and investigate what falls outside EU GMP ch. 6 §6.9, 6.35
Raise and close deviations EU GMP ch. 5 §5.15
Run CAPA through action and verification EU GMP ch. 1 §1.4(xiv)
Raise an incident and find the batches around it EU GMP ch. 8
Record a complaint from outside: who complained, what was answered, and what happened to the batch EU GMP ch. 8 §8.5–8.14
Run self-inspection to a programme EU GMP ch. 9
Approve and supersede procedures EU GMP ch. 4
Register counterparties and score suppliers EU GMP ch. 7
Compile the annual product quality review EU GMP ch. 1 §1.10
Recall released product EU GMP ch. 8 §8.22–8.30
Control packaging materials and their storage EU GMP ch. 5 §5.46
Clear the line before packing, and record it EU GMP ch. 5 §5.50
Issue, reconcile and destroy labels EU GMP ch. 5 §5.46, §5.61, §5.62
Record a batch that came back: from whom, how much, why, and what was done with it EU GMP ch. 5 §5.70
Assemble a batch dossier EU GMP ch. 4
Hold seed lots and cell banks as master and working generations, and count the passages between them and the product EU GMP Annex 2 §39, §40
Quarantine a new bank, characterise it and release it EU GMP Annex 2 §42
A container taken out of the bank never goes back in EU GMP Annex 2 §47
Act on donor health information that arrives after the material was taken EU GMP Annex 2 §36, §65
Say what makes a batch, and treat a product made for one patient as its own batch EU GMP Annex 2 §27
Test the primary containment on a schedule, and record that it still holds EU GMP Annex 2 §14
Test each batch of medium for growth promotion before it is used, and justify any reliance on the supplier EU GMP Annex 2 §51
Run formal change control EU GMP Annex 2 §48
Release in stages: transport under quarantine, then conditional certification, then final EU GMP Annex 2 §70
Act on a failing result that arrives after dispatch and before expiry EU GMP Annex 2 §70
Approve a specification, every limit naming its method EU GMP Annex 7 §8 · path step Annex 2 §42
Hold and monitor storage conditions EU GMP Annex 7 §4 · path step Annex 2 §45
Transfer custody by name, vehicle and receiver Lesotho LN40 reg. 23(2)(f) · path step Annex 2 §28, §36
Keep reference and retention samples EU GMP Annex 19 §3–4 · path step Annex 2 §20
Judge how far a supplier certificate can be trusted EU GMP Part II 7.31 · path step Annex 2 §26, §31
Qualify equipment through URS, IQ, OQ, PQ EU GMP Annex 15 §3 · path step Annex 2 §49
Print a label carrying the seven required fields Lesotho LN40 reg. 21(2) · path step Annex 2 §63
Take a sample to a sampling plan EU GMP Annex 7 §13, Part II 7.33 · path step Annex 2 §66
Release a batch EU GMP Annex 16 §1.6 · path step Annex 2 §70

Done by the site, recorded in MALUTI (4)ShowHide

Maintain buildings, floors, lighting, changing rooms EU GMP ch. 3 §3.2, §3.3, §3.31
Control pests in storage, by authorised people only EU GMP ch. 3 §3.4
Hold written contracts for outsourced work EU GMP ch. 7 §7.14–7.17
Clean equipment between tasks and account for the residue SAHPRA Annex A §5 · path step Annex 2 §57, §58

Outside the software (2)ShowHide

Examine a person medically and read the finding EU GMP ch. 2 §2.16
The examination is a doctor's work and the finding is medical. We hold the outcome in three words, the dates and who recorded them. A field for a diagnosis does not exist anywhere in this system, because a record that only ever grows cannot take a disclosure back.
Run the analysis itself EU GMP ch. 7
The laboratory has its own accreditation, its own methods and its own instruments. We hold the certificate and its hash, the limits it was judged against, the verdict, and the state of that laboratory's licence on the day it signed.

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Biological medicinal products step by step.

The path of a batch

Grown from a bank

Taken from a donor

Training is specific to what is grown here

A change in someone’s health keeps them out, and it is recorded

People do not walk from the live organisms to the rest

Everything grown comes from a master and a working generation

A new bank is quarantined, characterised and released

The bank has an inventory, and its cold is recorded continuously

What leaves the bank does not come back

The line runs from the donor to the point of use, and back

What the donor’s doctor learns later still reaches the product

Source animals are under a health programme, and it is recorded

A sick animal sends us back through everything it touched

A biological material carries its origin, not just its name

What counts as a batch is declared, not assumed

Critical parameters are identified, validated and held

Continuous monitoring belongs to the batch record

Treated product never meets untreated product

A product made for one person says whose it is

In-process control carries more weight here than at the end

An intermediate that waited is followed into the stability programme

Fourteen days or less: certified in two stages

Variability and change are reviewed on a period, not on a whim

What the rules ask, and what is built.

Not built yet (19)

Let’s map MALUTI to your site.